Role of Myokines in Myositis Pathogenesis and Their Potential to be New Therapeutic Targets in Idiopathic Inflammatory Myopathies

Abstract

Idiopathic inflammatory myopathies (IIM) represent a heterogeneous group of autoimmune diseases whose treatment is often a challenge. Many patients, even after immunosuppressive therapy, do not respond to treatment, so new alternatives have been sought for this. Therefore, other signaling pathways that could contribute to the pathogenesis of myositis have been investigated, such as the expression of myokines in skeletal muscle in response to the inflammatory process. In this review, we will refer to these muscle cytokines that are overexpressed or downregulated in skeletal muscle in patients with various forms of IIM, thus being able to contribute to the maintenance of the autoimmune process. Some muscle cytokines, through their antagonistic action, may be a helpful contributor to the disease modulation, and thus, they could represent personalized treatment targets. Here, we consider the main myokines involved in the pathogenesis of myositis, expressing our view on the possibility of using them as potential therapeutic targets: interleukins IL-6, IL-15, and IL-18; chemokines CXCL10, CCL2, CCL3, CCL4, CCL5, and CCL20; myostatin; follistatin; decorin; osteonectin; and insulin-like 6. An interesting topic regarding the complex connection between myokines and noninflammatory pathways implied in IIM has also been briefly described, because it is an important scientific approach to the pathogenesis of IIM and can be a therapeutic alternative to be considered, especially for the patients who do not respond to immunosuppressive treatment.

Myostatin and markers of bone metabolism in dermatomyositis

“…One of the key factors regulating myogenesis is myostatin (MSTN). Much interest has been given to this negative regulator of muscle mass and its inhibitor follistatin (FSTN) in physiologic as well as pathophysiologic conditions, including muscular dystrophies and inflammatory myopathies [for review see [ 5 ]]. Just like muscle metabolism, bone homeostasis also depends on the balance between positive and negative regulators.…”

Histological findings in skeletal muscle of SARS-CoV2 infected patient

“…Since the beginning of the SARS-CoV2 pandemic, there have been numerous studies showing, as our knowledge and understanding of the disease progressed, that this viral infection does not only affect lungs, heart, kidneys, liver, and other major organs but it involves the whole body, through both lesions specific to organs and by means of systemic inflammatory response to the viral infection. In the case of skeletal muscle, damage occurs directly by the cytopathic effect of the virus itself upon the target cell and by the elevated levels of cytokines, [12,13] being responsible for the neuromuscular symptomsmyalgia, weakness, asthenia, [14,15] and elevated serum levels of creatine kinases. [16,17]…”

Myokines and Resistance Training: A Narrative Review

“…Interleukin-6 (IL-6) was the first myokine that was discovered and is one of the most popular myokines discussed in several original data and reviews [ 6 , 7 , 11 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Years before the discovery of myokines, IL-6 was mentioned as an interferon (interferon beta2) [ 52 ].…”